Targeting tumor necrosis factor receptors in ankylosing spondylitis

• Published in: Annals of the New York Academy of Sciences 2019-04, Vol.1442 (1), p.5-16
• Main Authors: Lata, Michal, Hettinghouse, Aubryanna S., Liu, Chuan‐ju
• Format: Article
• Language: English
• Subjects: Animals; Ankylosing spondylitis; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Clinical trials; Humans; Inflammatory diseases; Inhibitors; Medical research; Necrosis; Pathogenesis; progranulin; Receptors; Receptors, Tumor Necrosis Factor - antagonists & inhibitors; Receptors, Tumor Necrosis Factor - metabolism; Signal Transduction; Spondylitis; Spondylitis, Ankylosing - drug therapy; Spondylitis, Ankylosing - metabolism; Therapy; TNF inhibitors; TNFR1; TNFR2; Tumor necrosis factor; Tumor necrosis factor receptors; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumors
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/nyas.13933

Over the past two decades, considerable advances in our understanding of inflammatory and immune pathways have allowed for the growing use of targeted biologic therapy. Most notably, the introduction of tumor necrosis factor (TNF) inhibitors has dramatically changed the management of autoimmune inflammatory disorders, including ankylosing spondylitis (AS). Despite the efficacy of TNF inhibitors documented in multiple clinical trials, anti‐TNF therapy in AS is far from foolproof; it is associated with serious adverse effects and limited response to therapy in some patients. Moreover, specific questions regarding the role of TNF as a mediator of AS remain unanswered. Therefore, additional efforts are needed in order to better understand the role of TNF in the pathogenesis of AS and to develop safer and more effective treatment strategies. The purpose of this review is to better the understanding of the physiologic and pathogenic roles of TNF signaling in the course of AS. Relevant TNF biology and novel approaches to TNF blockade in AS are discussed. Tumor necrosis factor (TNF) inhibitors have dramatically improved the management of autoimmune inflammatory disorders such as ankylosing spondylitis (AS). However, anti‐TNF therapy in AS can be associated with serious adverse effects and limited response to therapy. This review seeks to improve the understanding of the physiologic and pathogenic roles of TNF signaling in the course of AS. Relevant TNF biology and novel approaches to TNF blockade in AS are discussed.